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Author Spotlight: Exploring Autism Spectrum Disorder Symptoms in Fruit Flies &#8212; Genetic Models and Behavioral Tests
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Microbiota-Based Interventions Differentially Rescue Gut and Social Behavior Phenotypes in a Drosophila Autism-like

Natalia A Peta Martinez1, Melanie Reinoso Arnaldi1, Tasha M Santiago-Rodriguez2,3

  • 1Department of Biology, University of Puerto Rico Rio Piedras, San Juan, Puerto Rico, USA.

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Summary

KDM5 gene mutations in flies cause gut dysbiosis and social deficits. While some probiotics restore gut bacteria, only specific strains like Lactobacillus helveticus improved social behavior, highlighting the complexity of gut-brain communication in autism spectrum disorder.

Keywords:
FMTautism modeldrosophilagut-brain axismicrobiomeprobiotics

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Area of Science:

  • Neuroscience and Microbiology
  • Epigenetics and Gut-Brain Axis Research
  • Model Organism Research (Drosophila)

Background:

  • Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder often linked with gastrointestinal (GI) issues.
  • The gut microbiota-brain axis is implicated in the GI dysfunction contributing to neurological symptoms in ASD.
  • Loss-of-function mutations in KDM5 histone demethylases are associated with intellectual disability and ASD.

Purpose of the Study:

  • To evaluate microbiota-based interventions (probiotics, FMT) for modulating gut microbiota and behavior in a Drosophila KDM5 loss-of-function (KDM5LOF) model.
  • To investigate the role of KDM5 in regulating gut microbial composition and social behavior.
  • To determine if restoring gut microbial abundance is sufficient to rescue behavioral deficits.

Main Methods:

  • Utilized a Drosophila KDM5LOF model exhibiting ASD-like phenotypes.
  • Administered probiotic supplements (Lactiplantibacillus plantarum, Lactobacillus helveticus) and performed fecal microbiota transplantation (FMT).
  • Quantified bacterial abundance via CFU assays and 16S rRNA gene sequencing; assessed social behavior, anxiety, and locomotion.

Main Results:

  • KDM5 deficiency led to reduced gut Lactobacillus, Acetobacter, and Enterobacter species and impaired social behavior.
  • L. plantarum restored gut microbial abundance but not social behavior; L. helveticus improved social interaction without significantly altering bacterial abundance.
  • Fecal microbiota transplantation partially restored Lactobacillus, reshaped microbial communities, and improved social behavior in KDM5LOF flies.

Conclusions:

  • KDM5 is a key regulator of gut microbial viability and social behavior.
  • Microbiota-based interventions have strain- and phenotype-specific effects; microbial restoration alone is insufficient to rescue social behavior.
  • Drosophila serves as a valuable model for studying epigenetic regulation of microbiota-behavior relationships relevant to ASD.